Reaktion #60280

Reaktionsgleichung

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid methyl ester

K2CO3

methyl vinyl sulfone

→

pure desired product

Ausbeute 59.1%

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(2-methanesulfonyl-ethyl)-3H-benzoimidazole-5-carboxylic acid methyl ester

Ausbeute 59.1%

Lösungsmittel

DMF

ethyl acetate

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe layers are separated
2. 2
   Waschenthe organic layer is washed with water (3×) and brine
3. 3
   ExtraktionThe combined aqueous washes are extracted with ethyl acetate
4. 4
   TrocknenThe combined organic extracts are dried (MgSO4)
5. 5
   Einengenconcentrated under reduced
6. 6
   SonstigePurification
7. 7
   workup.DISSOLUTIONby dissolving the residue in methylene chloride
8. 8
   Sonstigeprecipitating with diethyl ether

Vorschrift

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid methyl ester 8b (1.55 g, 3.89 mmol) is dissolved in 15 mL DMF under N2. K2CO3 (0.70 g, 5.06 mmol) is added followed by methyl vinyl sulfone (0.41 mL, 4.67 mmol). After stirring 16 hours at room temperature, the reaction mixture is diluted with ethyl acetate and water. The layers are separated and the organic layer is washed with water (3×) and brine. The combined aqueous washes are extracted with ethyl acetate. The combined organic extracts are dried (MgSO4) and concentrated under reduced. Purification by dissolving the residue in methylene chloride and precipitating with diethyl ether, repeated several times, provides 1.16 g (59%) pure desired product as a yellow solid: MS APCI (+) m/z 506, 504 (M+Br pattern) and 400, 398 (M−methyl ethyl sulfone Br pattern).

Quelle